Dose Escalation Trial of CD40.HIVRI.Env Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Volunteers

Summary

FIRST PART: DOSE ESCALATION Multicenter double-blind placebo controlled phase I dose-escalation trial that will be conducted in France and Switzerland to evaluate different dose levels of CD40.HIVRI.Env (adjuvanted with Hiltonol) alone and in co-administration with DNA-HIV-PT123.

A total of 72 eligible healthy participants will be recruited into 6 groups. Within each group, participants will be randomized in a double blind manner to active intervention or placebo in a 5:1 ratio. Enrolment into a given group (other than group "Solo 0.3") will open sequentially depending on the " go-criterion " based on the safety data of the preceding group(s).

The primary objective is to assess the safety of three dose levels of CD40.HIVRI.Env (0.3; 1; 3 mg) adjuvanted with Poly-ICLC (Hiltonol®), alone and in combination with DNA-HIV-PT123, administered at weeks 0, 4 and 24 in healthy participants.

Secondary objectives are to assess the capacity of poly-ICLC-adjuvanted CD40.HIVRI.Env alone and in combination with DNA-HIV-PT123 to elicit immune responses against HIV (immunogenicity):

* Humoral (antibody) responses ;
* B-cell responses ;
* T-cell responses.

SECOND PART: BOOST VACCINATION AND FOLLOW-UP Preliminary safety results allow consideration of long-term follow-up and evaluation of an additional CD40.HIVRI.Env booster injection in volunteers. An admendment was approved to complete the follow-up with two visits: 2 weeks (WLB+02) and 24 weeks (WLB+24) after the boost (WLB). Volunteers who received the active strategy in the first part of the trial (n=60) will be randomized in a single blind design and will receive an additional 0.3 mg dose of CD40HIVRI.Env vaccine either combined with Hiltonol adjuvant, as in the first part of the trial, or unadjuvanted. Part 2 will take place after the W48 visit and the participant's unblinding of Part 1.

It will address the following secondary objectives:

* To evaluate tolerance
* To evaluate the evolution of long-term vaccine responses (immunogenicity) and the effect of a booster injection of CD40.HIVRI.Env alone or adjuvanted with Poly ICLC- Hiltonol®. The tests that will be performed will be identical to those performed during the first phase of the trial allowing the monitoring of the evolution of responses.

Conditions

• Healthy Adults

Interventions

BIOLOGICAL

Solo 0.3 group

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 0.3 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1 ml subcutaneous route in right deltoid at weeks 0, 4 and 24.

BIOLOGICAL

Solo 1 group

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 1.0 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1 ml subcutaneous route in right deltoid at weeks 0, 4 and 24.

BIOLOGICAL

Solo 3 group

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 3.0 and 1.0 mg/injection, i.e. 1.2 ml subcutaneous route in right deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1.2 ml subcutaneous route in right deltoid at weeks 0, 4 and 24.

BIOLOGICAL

Combi 0.3 group

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 0.3 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid; and combined with DNA-HIV-PT123 HIV-1 at 4.0 mg/injection, i.e. 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1 ml subcutaneous route in right deltoid and 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24.

BIOLOGICAL

Combi 1 group

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 1.0 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid; and combined with DNA at 4.0 mg/injection, i.e. 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1 ml subcutaneous route in right deltoid and 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24.

BIOLOGICAL

Combi 3 group

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 3.0 and 1.0 mg/injection, i.e. 1.2 ml subcutaneous route in right deltoid; and combined with DNA at 4.0 mg/injection, i.e. 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1.2 ml subcutaneous route in right deltoid and 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24.

BIOLOGICAL

Late boost CD40 alone

CD40.HIVRI.Env at 0.3 mg/injection, i.e. 1 ml subcutaneous route in right deltoid at week LB (late boost)

BIOLOGICAL

Late boost CD40 adjuvanted

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 0.3 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid at week LB (late boost)

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases

  lead OTHER_GOV

Principal Investigators

• Yves LEVY, Pr · Hopital Henri Mondor

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-03-29

Primary Completion

2024-11-29

Completion

2024-11-29

Countries

• France
• Switzerland

Study Locations